Project Summary/Abstract Most human cancers originate within the epithelium of hollow organs and ducts. Cancers that arise spontaneously from this thin layer of highly metabolically active tissue can be prevented using endoscopy to accurately localize and resect pre-malignant lesions that arise within large mucosal surfaces. We will form a Bioengineering Research Partnership (BRP) between the College of Engineering and the Medical School at the University of Michigan to develop a targeted endoscopic imaging strategy. This robust, well-characterized solution will enable rapid surveillance of cancer biomarkers expressed by the epithelium in hollow organs. We will scale down the dimensions of a prototype flexible fiber wide-field fluorescence endoscope from 3.6 to 2.4 mm. Thin-film PZT materials have high work density and will be used to reduce the size and packaging requirements for the scanner while maintaining high performance. Individual scanner legs will be actuated to perform random access control whereby arbitrary regions can be highlighted to maximize signal-to- noise ratio, contrast, and frame rate. We will optimize a panel of peptides specific for cell surface targets expressed early in epithelial-derived cancers. The peptides will be fluorescently-labeled with FITC, Cy5, and IRDye800, respectively, for multiplexed in vivo imaging. These fluorophores are excited at 488, 647, and 785 nm, respectively, and the spectra are non-overlapping. Specific binding will be validated using cells in vitro and human specimens ex vivo. We will verify the in vivo imaging performance of the 2.4 mm wide-field fluorescence endoscope in a pre-clinical model of colorectal cancer using implanted human adenoma organoids. These pre-cancerous lesions are flat and subtle in appearance, and express molecular targets with genetic heterogeneity at levels representative of those seen in human patients. Successful completion of these aims will result in a prototype instrument and peptide panel that can be clinically translated in the future to provide the research and medical community with new imaging tools for early cancer detection in hollow organs. This highly collaborative effort will be performed by a multi-disciplinary team of engineers, biochemists, and molecular biologists, and will be led by TD Wang, an expert in the development of peptide-based imaging agents and flexible fiber instruments, and by KR Oldham, an expert in microsystems technology.